Biomedical subjects

T W Wilson

Publications and source records attributed to T W Wilson.

At least 19 recordsLinked to original sources

PubMed2004

AGT and RH blood group polymorphisms affect blood pressure and lipids in Afro-Caribbeans.

Population blood pressure variation is most likely due to multiple genes. This is likely the reason why monogenic testing with the angiotensinogen (AGT) gene polymorphisms on chromosome 1 (1q42-43), especially M235T, has met with negative results, especially in those of African descent. The RH blood group system, also on chromosome 1 (1 p36.2-34), has likewise been associated with blood pressure variation in African-Americans and with the rise in blood pressure with age in whites. Using a random sample of the population, we investigated the combined effects of single and combined variation of the AGTN M235T and RH genotypes on blood pressure, lipids, and lipoprotein concentrations in Afro-Caribbeans aged 18-60 years from the island nation of Dominica. In monogenic analysis, AGT M235T was not associated with blood pressure. However, it was associated with HDL (MM 42+/-23, MT 44+/-12, TT 52+/-14 (P=0.002)). RH genotype was significantly associated with systolic blood pressure (P=0.006) and Apo-A (P=0.003). These effects remained after adjustment for age, gender, weight, and BMI. In the polygenetic analysis, AGT M235T and RH were significantly associated with systolic blood pressure (P=0.037; interaction effects, P=0.068). The association of the AGT M235T with blood pressure across RH blood group haplotypes was then tested. Of the five RH haplotypes available for analysis, the AGT M235T was significantly associated with blood pressure within the "D" haplotype (P=0.01). The RH blood group and gender were significantly associated with systolic blood pressure and Apo-A levels (P=0.005 and 0.012, respectively). All interactions were independent of age and weight. In conclusion, we demonstrate a significant association of AGT M235T with blood pressure and cholesterol metabolism in an Afro-Caribbean population in the "genetic context" of the RH blood group system. Further investigation of these interactions may help understand the effects of genetic factors on cardiovascular risk in African-derived and other populations.

Adult↗

PubMed2002

Accuracy of the Dinamap 1846 XT automated blood pressure monitor.

Accurate blood pressure (BP) measurement is important for the detection and treatment of hypertension. Despite widespread use of automated devices, there is limited published evidence for their reliability and accuracy. To determine the reliability and accuracy of the Dinamap 1846XT (Critikon Corporation, Tampa, FL, USA), a commonly used non-invasive oscillometric BP monitor The Dinamap was evaluated against the mercury manometer in 70 randomly selected adult hospitalised medical patients. Each individual underwent three sets of standardised BP measurement by automated method and three sets by mercury manometer by two independent observers. Reliability of BP measurement was assessed by repeated measures analysis. Dinamap accuracy was evaluated according to the American Association of Medical Instrumentation (AAMI) and British Hypertension Society (BHS) guidelines. Most patients were either normotensive or had stage I hypertension. The Dinamap tended to overestimate lower diastolic BP, and displayed poor reliability (P < 0.05). despite meeting aami guidelines, only 59% of systolic and 56% of diastolic dinamap readings were within 5 mm hg of the mercury manometer and 84% of systolic and 80% of diastolic readings were within 10 mm hg (bhs grade c). systolic and diastolic accuracy were worse with pressures >160/90 mm Hg (grade D) although these measures were based on a smaller sample of subjects. In conclusion the Dinamap yields inaccurate estimates of both systolic and diastolic BP even under standardised, and thus optimal conditions. This inaccuracy is exaggerated at higher BP (>160/90 mm Hg), although the number of measurements at higher pressures was small. We recommend that this device not be used when accurate BP measurement is needed for therapeutic decision-making.

Adult↗

PubMed2002

Effect of zeranol or melengestrol acetate (MGA) on testicular and antler development and aggression in farmed fallow bucks.

Fifteen yearling fallow bucks were randomly assigned by BW to one of three treatment groups: control (C; n = 5), melengestrol acetate (MGA; n = 5), and zeranol (Z; n = 5), to evaluate effects on testicular development, aggressive behavior, antler growth, sexual activity, ADG, and BW. Zeranol-treated bucks received zeranol ear implants (36 mg) at 90-d intervals, and MGA-treated bucks received MGA in the ration (100 microg x animal(-1) x d(-1)). Bucks grazed ryegrass/Coastal bermudagrass pasture and were supplemented with 3:1 corn/soybean meal at 0.45 kg x animal(-1) x d(-1). Body weights, body condition scores (BCS), blood samples, and testis measurements were obtained at d 0 and at 14-d intervals for 229 d. As bucks reached hard antler (7/15 to 8/25), antlers were harvested and weighed, and ejaculates were collected at 14-d intervals. Aggression was evaluated using 10-min video sessions scoring body blows, avoidance, head pushes, and head bunts. Scrotal circumference (SC) and paired testis volume were affected by a day x treatment interaction (P < 0.01); testes of zeranol-treated bucks were smaller than those of control or MGA-treated bucks. First sperm in the ejaculate tended to be delayed (P < 0.10) in zeranol-treated bucks compared with control and MGA-treated bucks. Melengestrol acetate-treated bucks had a maximum sperm concentration in the ejaculate that was three times (P < 0.05) that of control bucks and nine times (P < 0.05) that of zeranol-treated bucks. Antler weight was the least (P < 0.01) for bucks receiving zeranol and greatest (P < 0.10) for MGA-treated bucks; intermediate values were recorded for the control bucks. Aggressive behavior was delayed (P < 0.05) for zeranol-treated bucks until treatment effects were overcome. Melengestrol acetate-treated bucks had decreased (P < 0.01) aggressive behavior compared with control bucks. Melengestrol acetate-treated bucks had increased (P < 0.05) serum testosterone concentrations compared with control and zeranol-treated bucks. Human chorionic gonadotropin-stimulated peak serum testosterone concentrations for zeranol-treated bucks were delayed (P < 0.01) compared with control and MGA-treated bucks. Although zeranol-treated bucks overcame treatment effects, they were never able to reach testicular measurements or sperm concentrations equal to those of the control or MGA-treated bucks. Zeranol and MGA treatments may have both positive and negative effects that can be utilized when producing slaughter bucks.

Aggression↗

PubMed2001

Binge drinking among undergraduate college students in the United States: implications for other substance use.

The authors examined the relationship between binge drinking and other substance use among US college students, using nationally representative data from the 1995 National College Health Risk Behavior Survey implemented by the Centers for Disease Control and Prevention. Compared with nonbinge drinkers, current binge drinkers were significantly more likely to report "ever" using and current use of cigarettes, marijuana, cocaine, and other illegal drugs. The researchers also found that the more often students binge drank, the more likely they were to have ever used cigarettes, marijuana, cocaine, and other drugs, and the more likely they were to report current use of cigarettes and marijuana. Those who design programs to prevent binge drinking and use of other substances should take into account the reality that many students use more than one substance and that the more frequently students report binge drinking, the more likely they are to be using other substances as well.

Adolescent↗

PubMed2001

Cysteinyl leukotrienes mediate enhanced vasoconstriction to angiotensin II but not endothelin-1 in SHR.

We assessed whether cysteinyl leukotrienes mediate the vasoconstrictor responses to angiotensin II and endothelin-1 in the mesenteric vascular bed of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) perfused ex vivo at a constant flow rate of 5 ml/min with Krebs buffer. Maximal perfusion pressure response (E(max)) but not EC(50) values to angiotensin II (P < 0.001) and endothelin-1 (P < 0.01) were significantly higher in the SHR, whereas the responses to potassium chloride remained unchanged. Inclusion of the selective 5-lipoxygenase inhibitor AA-861 or the cysteinyl leukotriene receptor antagonist MK-571 significantly reduced the vasoconstrictor responses to angiotensin II but not to endothelin-1 and potassium chloride. The reduction in E(max) to angiotensin II was more pronounced in SHR (P < 0.001) than in WKY (P < 0.05) rats. Cysteinyl leukotrienes LTC(4)-, LTD(4)-, and LTE(4) (1 microM)-evoked vasoconstrictor responses were significantly higher in SHR (P < 0.05), whereas LTB(4) failed to evoke any response in either strain. These data suggest that 5-lipoxygenase metabolites, particularly cysteinyl leukotrienes, contribute to the exaggerated vasoconstrictor responses to angiotensin II but not to endothelin-1.

Angiotensin II↗

PubMed2001

Endothelin antagonist reduces hemodynamic responses to vasopressin in DOCA-salt hypertension.

The contribution of endothelin to the changes in blood pressure, cardiac output, and total peripheral resistance evoked by arginine vasopressin and angiotensin II was investigated in deoxycorticosterone acetate (DOCA)-salt hypertensive rats by infusing the peptides intravenously before and after pretreatment with the endothelin receptor antagonist bosentan. Blood pressure was recorded with radiotelemetry devices and cardiac output was recorded with ultrasonic transit time flow probes in conscious unrestrained animals. The dose-related decreases in cardiac output induced by vasopressin and angiotensin II were unaffected by bosentan. In contrast, the dose-related increases in total peripheral resistance evoked by vasopressin were blunted in both DOCA-salt hypertensive and sham normotensive rats, but this effect of bosentan was greater in the DOCA-salt hypertensive group. In contrast with vasopressin, bosentan failed to change hemodynamic responses to angiotensin II. The exaggerated vascular responsiveness (total peripheral resistance) of the DOCA-salt hypertensive group to vasopressin was largely abolished by bosentan. These results suggest that endothelin contributes to the hemodynamic effects of vasopressin but not angiotensin II in the DOCA-salt model of hypertension.

Angiotensin II↗

PubMed2001

Insulin-induced biphasic responses in rat mesenteric vascular bed: role of endothelin.

The vasodilatory capacity of insulin has been widely reported, yet some investigators have not noted this effect. Because insulin has been shown to enhance endothelin release, we speculated that endothelin could be attenuating insulin-evoked vasodilation. We examined the effect of ex vivo insulin perfusion on vascular resistance by using the Sprague-Dawley rat mesenteric vascular bed. In methoxamine-preconstricted preparations, insulin (3.0 pmol/L to 10 nmol/L) evoked a concentration-dependent decrease in perfusion pressure (PP) with a maximal response of 42.0+/-9.2%, whereas continuous exposure to 10 nmol/L insulin induced a 51.8+/-3.5% relaxation. Further exposure to 10 nmol/L insulin resulted in the generation of endothelin and a subsequent loss of the vasodilatory response. Indomethacin had no effect on vascular responses. The vasodilatory response was significantly inhibited by nitric oxide synthase inhibition (20.5+/-4.2%; P<0.01) and calcium-activated potassium channel blockade (28.5+/-3.7%; P<0.05). Endothelial denudation attenuated the vasodilatory component (20.3+/-7.1%; P<0.01) and altered the biphasic pattern of the response. The decline in insulin-evoked vasodilation was significantly prevented by an endothelin-A antagonist (BQ123), an endothelin-B antagonist (BQ788), and nonselective endothelin blockade with both BQ123 and BQ788. These results demonstrate that the endothelium is intimately involved in regulating the vascular response to insulin. Insulin promotes the release of nitric oxide and endothelium-derived hyperpolarizing factor. During sustained exposure to higher concentrations, this vasodilatory effect is countered by the pathological generation of endothelin. Endothelin receptor blockade facilitates the maintenance of vasodilation despite high insulin concentrations.

Animals↗

PubMed2001

Substance use on school property among students attending alternative high schools in the United States.

We analyzed nationally representative data from the 1998 National Alternative High School Youth Risk Behavior Survey, conducted by the Centers for Disease Control and Prevention, to determine the prevalence of substance use on school property among alternative high school students in the United States, to describe the characteristics of students who use substances on school property, and to examine the interrelationships of substance-use behaviors. During the 30 days preceding the survey, nearly 48 percent of students used at least one substance on school property and 17 percent used more than one substance on school property. Males were more likely than females and white students were more likely than black or Hispanic students to have used substances on school property. The results of this and other studies suggest that school administrators, public health practitioners, and policy makers should work to improve strategies for reducing substance use in this heterogeneous, hard-to-reach population.

Adolescent↗

PubMed2001

The 2000 Canadian recommendations for the management of hypertension: part two--diagnosis and assessment of people with high blood pressure.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of high blood pressure in adults. OPTIONS: For people with high blood pressure, the assignment of a diagnosis of hypertension depends on the appropriate measurement of blood pressure, the level of the blood pressure elevation, the duration of follow-up and the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases. For people diagnosed with hypertension, defining the overall risk of adverse cardiovascular outcomes requires laboratory testing, a search for target organ damage and an assessment of the modifiable causes of hypertension. Out-of-clinic blood pressure assessment and echocardiography are options for selected patients. OUTCOMES: People at increased risk of adverse cardiovascular outcomes and were identified and quantified. EVIDENCE: Medline searches were conducted from the period of the last revision of the Canadian recommendations for the management of hypertension (May 1998 to October 2000). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the identification of people at increased risk of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: The identification of people at higher risk of cardiovascular disease will permit counselling for lifestyle manoeuvres and the introduction of antihypertensive drugs to reduce blood pressure for patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to aspects of the diagnosis and assessment of patients with hypertension, including the accurate measurement of blood pressure, criteria for the diagnosis of hypertension and recommendations for follow-up, routine and optional laboratory testing, assessment for renovascular hypertension, home and ambulatory blood pressure monitoring, and the role of echocardiography in hypertension. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only the recommendations achieving high levels of consensus are reported here. These guidelines will be updated annually. ENDORSEMENT: These recommendations are endorsed by the Canadian Hypertension Society, The Canadian Coalition for High Blood Pressure Prevention and Control, The College of Family Physicians of Canada, The Heart and Stroke Foundation of Canada, The Adult Disease Division and Bureau of Cardio-Respiratory Diseases and Diabetes at the Centre for Chronic Disease Prevention and Control of Health Canada.

Adrenal Gland Neoplasms↗

PubMed2000

Altered paracrine effect of endothelin in blood vessels of the hyperinsulinemic, insulin resistant obese Zucker rat.

OBJECTIVE: Earlier, we reported that high insulin incubation in vitro leads to increased ETA receptor expression in cultured rat aortic smooth muscle cells (Diabetes 1998, 47: 934-944). Our later observation of enhanced endothelin-1 evoked vasoconstriction in aorta from the hyperinsulinemic obese Zucker rat indicated that this interaction might also be relevant in vivo. To further examine the relationship between insulinemia and endothelin, we characterized endothelin receptor expression and endothelin-1 peptide levels in vascular tissues and plasma from young and old obese Zucker rats. METHODS: 12 and 40-week-old Zucker obese and lean rats were used. Plasma endothelin-1 levels and endothelin-1 peptide content in the mesenteric artery and in the thoracic aorta were examined by radioimmunoassay. Messenger RNA levels of endothelin-1 peptide and ETA and ETB receptors were examined in the aortic and mesenteric vessels using RT-PCR. RESULTS: Obese rats from both age groups had significantly higher plasma levels of insulin (4-10 fold), total cholesterol (2-3 fold), triglycerides (10-fold), and glucose (approximately 1.5 fold) than their lean counterparts. There was a trend toward worsening lipoproteinemia and glycemia, but improved insulinemia with age in the obese rats. In association with these changes, obese rats exhibited attenuated endothelin-1 peptide and preproET-1 mRNA levels, but conversely elevated ETA and ETB receptor mRNA levels in both aortic and mesenteric vessels. CONCLUSION: These data suggest that vascular tissue from the metabolically dysregulated obese Zucker rat exhibits attenuated endothelin-1 peptide production and elevated endothelin receptor levels. Since elevated insulin levels have been linked to increased endothelin receptor expression, it is plausible that hyperinsulinemia upregulates endothelin receptors contributing to elevated vasoconstrictor responses to endothelin-1 in this model of obesity and hypertension.

Animals↗

PubMed2000

Effect of losartan on angiotensin II-mediated endothelin and prostanoid excretion in humans.

Angiotensin II (Ang II) stimulates renal prostanoid and vascular endothelin-1 (ET-1) release. Most known Ang II effects are mediated by AT1 receptors. Our aim was to determine whether AT1 receptor activation mediates Ang II-evoked renal prostanoid and ET-1 release. Eleven healthy men were randomized in a crossover, double-blind fashion to receive 100 mg/day of losartan or matching placebo, for 8 days. Blood and urine were sampled before and after a 2-h infusion of Ang II at a rate previously determined to increase mean arterial pressure (MAP) by 25 to 30 mm Hg in each subject. After a 14-day washout, subjects received the alternate treatment. Pretreatment with losartan had little effect on baseline MAP, but increased plasma renin activity, and virtually eliminated the pressor response to Ang II infusion. Angiotensin II significantly increased prostanoid excretion after placebo; the prostanoid response to Ang II was even greater after losartan. Plasma ET-1 was not altered by Ang II infusion, with or without losartan. In contrast, urine ET-1 excretion rate decreased to 40% of baseline after Ang II but not after losartan pretreatment; losartan alone had no effect. We conclude that Ang II decreases renal ET-1 synthesis and release through the AT1 receptor. In contrast, Angiotensin II-mediated renal prostanoid synthesis does not require activation of AT1 receptors. These findings indicate that AT1 receptor antagonists could provide renal protection through indirect mechanisms.

Adult↗

PubMed2000

Fenofibrate lowers blood pressure in two genetic models of hypertension.

Fenofibrate, a commonly used lipid lowering drug, induces the expression of the gene coding for cytochrome P450-4A, whose major product is 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE, a potassium channel antagonist, could increase or decrease blood pressure (BP). We studied the effects of four weeks of oral fenofibrate on BP, urine output (UVol), plasma renin activity (PRA), and urine protein excretion in young (4-5 weeks) stroke prone spontaneously hypertensive rats (SHRSP), older (25 weeks) SHRSP, Dahl salt sensitive rats (Dahl S) on a high salt diet, Dahl S rats on a normal salt diet, and normotensive Sprague-Dawley (SD) rats. Fenofibrate prevented the increase in BP in 4-5 week old SHRSP, reduced BP in 25 week old SHRSP, but had no effect on BP in normotensive SD rats. Similarly, fenofibrate prevented the increase in BP in Dahl S rats on a high salt diet, but had no effect in Dahl S rats on a low salt diet. Fenofibrate increased UVol (and reduced weight gain) in young SHRSP and tended to increase it in other groups. It also increased PRA 2 to 5-fold in all groups except older SHRSP. Young SHRSP receiving fenofibrate excreted significantly less urine protein than control rats. The drug reduced proteinuria in Dahl S rats on high salt diet, but had no significant effect on proteinuria in other groups. In summary, fenofibrate reduced blood pressure and weight gain, increased UVol and PRA, and reduced urine protein excretion in young SHRSP. Other groups of animals showed these changes to a variable, but directionally similar extent. These findings are consistent with a natriuretic effect of fenofibrate.

Animals↗

PubMed1999

Prevalence and predictors of white-coat response in patients with treated hypertension.

BACKGROUND: White-coat response, defined as higher office blood pressure readings than ambulatory readings, is common. Few studies have estimated its prevalence among subjects with treated hypertension, and almost none have defined its determinants. The objective of this study was to estimate the prevalence of white-coat response among subjects with treated hypertension and to determine whether the phenomenon could be predicted using clinical and psychometric data. METHODS: A total of 103 treated patients (55 men and 48 women) with uncontrolled hypertension who attended a hypertension outpatient clinic in Saskatoon between September 1993 and December 1995 were entered into the study. Patients had at least 2 clinic blood pressure readings of 140/90 mm Hg or higher, had no target organ damage or left ventricular hypertrophy, and had been prescribed 2 or more classes of antihypertensive drugs. Patients had blood pressure measured in the supine position in the clinic, were placed on 24-hour ambulatory blood pressure monitoring and then completed questionnaires before returning to the clinic. Patients were classified as exhibiting a white-coat response if their mean daytime ambulatory systolic/diastolic blood pressure was 139/89 mm Hg (both) or less, or if the systolic/diastolic pressure was at least 20/15 mm Hg (both) lower than the clinic reading. RESULTS: Eleven men (20%, 95% confidence interval [CI] 10%-33%) and 26 women (54%, 95% CI 39%-69%) showed white-coat response. Logistic regression modelling showed that determinants such as stress had significantly different effects among men and women. Separate models were therefore created for men and women. For women, perceived level of stress was the most important predictor of white-coat response (odds ratio [OR] per unit 7.0, 95% CI 1.3-36.0), followed by time since diagnosis. For men, depression was a weak predictor, with higher depression scores predicting sustained hypertension (OR per unit 1.2, 95% CI 1.01-1.5). INTERPRETATION: Sex is an important factor in white-coat response. Attempts to predict white-coat response from psychometric variables should take sex differences into account. Clinical variables were not effective as predictors of white-coat response.

Blood Pressure↗

PubMed1999

A cardiovascular risk factor reduction clinic.

OBJECTIVE: To describe a cohort of patients referred to a cardiovascular risk factor reduction unit (CRFRU). DESIGN: Prospective cohort study. SETTING: Out-patients referred to a specialty clinic in a tertiary care hospital. PATIENTS: Seven hundred and four consecutive male and female patients with one or more cardiovascular risk factors, of whom 388 were reassessed after one year. INTERVENTIONS: Standard risk factors were measured in all participants. The probability of coronary artery disease (CAD) was assessed according to the Framingham equation and results were compared with data from the Saskatchewan Heart Health Survey for the general population of Saskatchewan. Patients received dietary and fitness advice, as well as drug therapy when indicated. For follow-up studies, the change in probability of CAD and selected variables after one year were measured. MAIN RESULTS: Patients referred to the CRFRU were at considerably higher risk for CAD than the general population. One hundred and sixty-eight of 235 men and 77 of 153 women seen in follow-up had a reduced risk score. Those who improved had a favourable change in systolic blood pressure and in their lipid profile, as well as greater weight loss. CONCLUSIONS: A CRFRU is feasible and appears to reduce risk in a considerable proportion of patients.

Adolescent↗

PubMed1998

Sudden death in a patient with chronic lymphocytic leukemia.

The authors describe a 51-year-old man with chronic lymphocytic leukemia who presented with respiratory distress and then died suddenly while in hospital. Autopsy revealed pulmonary leukostasis and a large intracardiac mass containing mostly mature lymphocytes and fibrin. Although leukostasis and lymphocyte thrombi have been described (albeit rarely) in chronic lymphocytic leukemia, an intracardiac "clot" has not. It seems plausible that this intracardiac mass caused the patient's death.

Embolism↗

PubMed1998

The antihypertensive efficacy of losartan and amlodipine assessed with office and ambulatory blood pressure monitoring. Canadian Cozaar Hyzaar Amlodipine Trial Study Group.

BACKGROUND: Losartan potassium is a recently marketed angiotensin II receptor antagonist. Previous studies have suggested that its full antihypertensive efficacy may be delayed for up to 12 weeks. The authors compared the antihypertensive efficacy and tolerability of losartan at 6 and 12 weeks with those of amlodipine besylate, a commonly used calcium antagonist. METHODS: This multicentre, randomized, double-blind clinical trial studied 302 patients with mild or moderate hypertension in 1995. Of the 302, 97 also underwent ambulatory blood pressure monitoring (ABPM). After a 4-week placebo run-in period, the patients were randomly assigned to group A, B or C for 12 weeks. Those in groups A and B began treatment with losartan at 50mg/d, and those in group C began with amlodipine at 5 mg/d. If the blood pressure remained uncontrolled after 6 weeks, subjects in group A had their losartan dose doubled (to 100 mg/d), those in group B were given hydrochlorothiazide (12.5 mg/d) in addition to the losartan, which remained at 50 mg/d, and patients in group C had their amlodipine dose doubled (to 10 mg/d). RESULTS: At 12 weeks all 3 regimens reduced office-recorded diastolic blood pressure (DBP) with the patient sitting. The mean reduction in group A was 8.7 mm Hg (95% confidence interval [CI] 7.3 to 10.1) (p < 0.001), in group B 12.5 mm Hg (95% CI 11.0 to 14.0) (p < 0.001) and in group C 12.9 mm Hg (95% CI 11.4 to 14.5) (p < 0.001). Losartan alone lowered sitting DBP to a lesser degree than the other 2 treatments (p < 0.01). In contrast, ABPM readings, whether 24-hour, daytime or nighttime, were not different among the regimens. Comparison of the results at 6 weeks yielded similar findings. Adverse effects were uncommon and were not different among the groups, with the exception of ankle edema, which was more frequent in group C. INTERPRETATION: Losartan alone reduces both office and ABPM readings. The observed changes in office-recorded sitting DBP suggest that losartan is less effective than amlodipine or the combination of losartan and hydrochlorothiazide, but ABPM did not confirm this difference. Perhaps changes in office readings measure different attributes of a drug than does ABPM.

Adolescent↗

PubMed1998

Insulin and vanadate restore decreased plasma endothelin concentrations and exaggerated vascular responses to normal in the streptozotocin diabetic rat.

Although insulin has been shown to raise plasma concentrations of endothelin (ET) and up regulate vascular smooth muscle ETA receptor expression, the interaction of vanadate, an insulinomimetic agent, with the vascular ET system has not been investigated. We compared the effects of oral vanadate treatment (0.5 mg/ml; p.o.) and insulin infusion (12 mU.kg-1.min-1 s.c.) for two weeks on plasma ET concentrations and vascular responses to endothelin-1 (ET-1) and the alpha-1 adrenoceptor agonist, methoxamine, in aortic ring preparations from streptozotocin (STZ) diabetic and non-diabetic adult male Sprague-Dawley rats. Plasma ET concentrations were lower (p < 0.01) in STZ diabetic rats compared with normal control rats. Insulin and vanadate treatment restored plasma ET to normal (p < 0.01) in STZ rats and increased ET concentrations in the control (p < 0.05) group. Higher maximal tension responses to both ET-1 (p < 0.01) and methoxamine (p < 0.05) were present in STZ rats in both endothelium intact and denuded aortic preparations compared with the control group. Both insulin and vanadate treatment returned these responses to normal. It is concluded that low plasma concentrations of insulin and high plasma glucose in STZ diabetic rats are accompanied by lower concentrations of plasma ET. Insulin and vanadate treatment restores diminished plasma ET to control concentrations and attenuates exaggerated agonist(s)-evoked vascular smooth muscle responses in STZ-induced diabetic rats. In addition to well known beneficial metabolic effects, insulin and vanadate may beneficially affect cardiovascular regulation in the STZ diabetic rat by correcting abnormal ET activity.

Animals↗

PubMed1998

Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension.

Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over placebo were observed in trough seated blood pressure with all irbesartan doses > or = 50 mg. These reductions reached statistical significance versus placebo within 2 weeks with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated with dose. Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT1 receptor blockade. In patients not controlled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no dose-related toxicity. Irbesartan, administered alone or in combination with HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe antihypertensive agent for the treatment of mild-to-moderate hypertension.

Aged↗